Heterogeneity of regional redox status and relation of the redox status to oxygenation in a tumor model, evaluated using electron paramagnetic resonance imaging.
Heterogeneity of regional redox status and relation of the redox status to oxygenation in a tumor model, evaluated using electron paramagnetic resonance imaging.
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DOI：
10.1158/0008-5472.can-09-4369
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发表时间：
2010-05-15
期刊：
影响因子：
11.2
通讯作者：
Ikota N
中科院分区：
文献类型：
--
作者：
Takeshita K;Kawaguchi K;Fujii-Aikawa K;Ueno M;Okazaki S;Ono M;Krishna MC;Kuppusamy P;Ozawa T;Ikota N
氧化还原状态沿着氧分压（pO 2）被广泛接受，其决定了用于治疗肿瘤的一些治疗方法（包括放射）的功效。据报道，通过硝酰基探针的还原来评价氧化还原状态在小鼠肿瘤模型中是异质的。然而，无论是在小鼠之间的氧化还原状态的异质性的变化，也没有氧化还原状态的关系，以pO 2在肿瘤已充分的特点。在本研究中，在i. v.注射组织渗透性硝酰基探针HM-PROXYL后，使用连续三维电子顺磁共振（EPR）成像评价了小鼠辐射诱导的纤维肉瘤肿瘤模型中的区域减少状态。HM-PROXYL信号的区域衰减遵循一级动力学，并且在6只小鼠中肿瘤中的降低率幅度和异质性程度各不相同。组织pO 2使用EPR血氧测定法与酞菁锂（LiPc）微晶植入肿瘤内进行测量。用EPR成像确定LiPc的位置。通过选择不与LiPc信号重叠的HM-PROXYL信号峰，在注射HM-PROXYL后获得连续图像，甚至在LiPc植入后也是如此。在13只荷瘤小鼠中，发现pO 2测量区域的pO 2和还原率之间的关系较低（r = 0.357），表明氧合程度不一定影响空气呼吸条件下的氧化还原状态。结果强烈表明，在每个肿瘤中的氧化还原状态和氧合的测量来表征肿瘤生理学的必要性。
It is widely accepted that redox status, along with the partial pressure of oxygen (pO2), determines the efficacy of some therapeutic methods applied to treat tumors, including radiation. Redox status, evaluated by the reduction of a nitroxyl probe, was reportedly heterogeneous in a mouse tumor model. However, neither variation of heterogeneity of the redox status among mice nor the relation of the redox status to pO2 in tumors has been characterized sufficiently. In this study, the regional reduction status in a mouse radiation-induced fibrosarcoma tumor model was evaluated using sequential three-dimensional electron paramagnetic resonance (EPR) imaging after i.v. injection of a tissue-permeable nitroxyl probe, HM-PROXYL. The regional decay of HM-PROXYL signal obeyed first-order kinetics, and the amplitude of the reduction rate and extent of its heterogeneity in a tumor varied among six mice. The tissue pO2 was measured using EPR oximetry with lithium phthalocyanine (LiPc) microcrystals implanted within the tumor. The location of LiPc was determined with EPR imaging. A sequential image was obtained following the injection of HM-PROXYL, even after LiPc implantation, by choosing an HM-PROXYL signal peak which does not overlap with the signal of LiPc. The relationship between pO2 and the reduction rate at the region of pO2 measurement was found to be low (r = 0.357) in 13 tumor-bearing mice, indicating that the extent of oxygenation does not necessarily affect the redox status under air-breathing conditions. The results strongly indicate the necessity of measurements of both redox status and oxygenation in every tumor to characterize tumor physiology.